Quality control has long been a necessary and routine procedure in clinical hematology. Accuracy in the counting of various types of blood cells is dependent, in part, upon the use of adequate control products and methods of using the control products. With the numerous types of equipment for particle counting now available, quality control by the use of control products is necessary, since the possibility of an instrument malfunctioning is ever present. The traditional method of maintaining a quality control program for automatic particle counting equipment has consisted of providing fresh human blood as a whole blood standard. However, this fresh blood is usable for only one day, therefore, various manufactured control products which have longer product lifetime have been developed.
Commonly used particles in a control product simulate or approximate the types of particles or cells that are intended to undergo analysis. Consequently, these particles are often referred to as analog particles. The analog particles are selected or designed so that they have certain characteristics that are similar to those of the particles or cells to be analyzed in the instruments. Exemplary characteristics include similarities in size, volume, surface characteristics, granularity properties, light scattering properties and fluorescence properties.
Various commercial reference control products are now available, which use various processed or fixed human or animal blood cells as analogs of human blood cells. U.S. Pat. No. 5,512,485 (to Young et al) teaches a hematology control comprising several white blood cell analogs made of processed and fixed animal nucleated blood cells. These white blood cell analogs are designed to have characteristics similar to subpopulations of white blood cells. Commercially available hematology controls can also contain red blood cell, platelet, reticulocyte and nucleated red blood cell components, and many of them are made of cellular analogs. Furthermore, certain non-nucleated red blood cells, such as human, turkey, and shark red blood cells, have been used for making analogs of white blood cell subpopulations for hematology reference controls, such as those described in U.S. Pat. No. 4,704,364 (to Carver et al).
The control products have been used to determine whether an instrument is properly functioning according to manufacturer's specifications. These control products can be divided into two types. The first type is an integrated control which contains more than one type of cellular components, for example, red blood cell, white blood cell and platelet components. Commercial examples of the first type of control products include Beckman Coulter, Inc.'s COULTER® 4C® Cell Controls and Streck Laboratories, Inc.'s Para 12® Cell Controls. These products are typically configured in three levels, i.e., normal, abnormal high and abnormal low, which simulate commonly seen normal and clinically abnormal blood samples. However, these integrated controls can not be used to test and verify the entire reportable ranges for various measurements of the hematology analyzers, because the concentrations of individual components are not sufficiently high or low. It is known that increasing concentration of components creates problems because of aggregation of cellular particles in the integrated control product.
Consequently, the second type of control products have been developed, which are specifically designed for testing the reportable range of various measurements on hematology analyzers and determine linearity of the reported parameters. The second type of control products typically contain a single blood cell component, such as white blood cell analog only or platelet analog only, at various concentrations over reportable range of a particular instrument. In this manner the problems associated with integrated controls that contain more than one type of blood cell components is avoided to a certain degree. Examples of the second type of control products include Streck Laboratories CVA products and R&D Systems CBC-Line Linearity Kits.
However, the existing control products of the second type have various deficiencies. First, using the single component linearity controls for determining linearity of measurements of several hematology parameters are time consuming and labor intensive. Currently, red blood cell count, white blood cell count, platelet count, and hemoglobin concentration are the reportable parameters most frequently subjected to confirmation of linearity of their measurements. Typically, five to eight control compositions with various concentrations are required for testing the entire reportable range for each reportable parameter. Consequently, the existing linearity control kit contains a substantial number of control vials, for example, more than 20 control vials for linearity determinations of the four parameters mentioned above. Commonly, it takes more than one hour for testing all control vials of a linearity control kit.
Secondly, at high concentrations the individual blood cell components still tend to aggregate or clump together causing difficulty in using the product. The aggregation has been found to occur especially at high concentration of white blood cell analogs. Before using these control products, vigorous agitation has been required to disperse the cellular particles. This is time consuming, which typically takes several minutes for mixing and settling the WBC controls prior to being used on the instrument to be tested. Moreover, vigorous agitation can be deleterious to the cellular components in the control composition, as such the existing linearity control kits commonly require different mixing procedures for different cell components. For example, in R&D Systems CBC-Line Linearity Kits each tube of the WBC & PLT controls is required to be mixed by vortexing for 2 minutes, then settling for 10 minutes to allow dissipation of microbubbles, and rapidly inverting 8 to 10 times immediately before use on the instrument; while the RBC controls are required to be mixed by manual rotations of the tubes between palms, without vortex or mechanical mixing.
Still further, some of the second type of control products are provided as a single component concentrate which requires manual dilution by the operator. This not only requires further time in preparing the control compositions prior to the test of the instrument, and it also introduces additional errors to the measurements. In this case, the reference values are established by the operator based on the dilution, which are not regulated by the manufacturer of the control products.
Consequently, there is a strong need for improved linearity control compositions and an improved linearity control system that solves one or more of these problems.